GENOME ENGINEERING CORE ABSTRACT The goal of the Genome Engineering Core of the Washington University Rheumatic Diseases Research Resource-based Center (WU-RDRRC) is to provide access to innovative genomic technologies to facilitate modeling and investigation of human rheumatic disease by WU-RDRRC investigators. Genomic investigation of the basis of rheumatic disease has become widespread, including genome-wide association studies (GWAS), whole exome and genome sequencing, and epigenetic profiling. However, the translation of genetic findings can be challenging, often requiring validation in unique model systems. Development of such models is now possible with state-of-the-art genome engineering technologies. These technologies, such as development of genetically-engineered mice and CRISPR/Cas9 editing of induced pluripotent stem cells (iPSCs) require significant experience and, in some cases highly-specialized equipment not available within most laboratories. We propose to support the ability of WU-RDRRC members to utilize the latest in genomic engineering techniques by leveraging services from the Transgenic and Knockout Mouse Facility (TKMF) and the Genome Engineering and iPSC Center (GEiC). Towards this end we propose the following Specific Aims: 1. Sustain, develop, and introduce new state-of-the-art genetics services to WU-RDRRC members. 2. Assist investigators in the generation of genetically engineered mouse models by partnering with the Transgenic and Knockout Mouse Facility (TKMF). 3. Assist investigators in the generation of CRISPR reagents for genetically-engineered mice and creation of genetically-engineered cell lines and stem cells including iPSCs by leveraging the Genome Engineering and iPSC Center (GEiC).